Responses of the Systemic Circulation and of the Renin—Angiotensin—Aldosterone System to Ketanserin at Rest and Exercise in Normal Man

Abstract

The systemic circulation at rest and during exercise was studied in ten normal male volunteers, after placebo on one occasion and after acute intravenous administration of the serotonergic antagonist ketanserin on another occasion. The effects of ketanserin on the components of the renin-angiotensin-aldosterone system, on plasma catecholamines and on exercise capacity for graded uninterrupted exercise were also investigated. At rest in recumbency rapid intravenous injection of 10 mg of ketanserin, followed by a continuous infusion of 2 mg/h, produced an acute but transient fall in mean intra-arterial pressure of 6 mmHg compared with placebo. After 15 min the mean arterial pressure with ketanserin was within 2 mmHg of the mean pressure with placebo. In the sitting position both at rest and up to 30% of maximal work rate, the mean arterial pressure during ketanserin did not differ from the pressure on placebo. However, at higher levels of physical activity the rise in mean arterial pressure was lower with ketanserin; the pressure achieved with placebo was 7.5 mmHg higher at maximal work rate. Heart rate and cardiac output were significantly higher during ketanserin. When the subjects were lying down and resting, plasma noradrenaline and adrenaline levels, plasma renin activity and angiotensin II concentration were not affected by ketanserin; however, these values were higher in the sitting position both at rest and during exercise. Plasma aldosterone was reduced by ketanserin during exercise and also when the subject was resting in the recumbent position.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Pharmacokinetics of Ketanserin

“…These values, in fact, agree closely with those found in practice, either in healthy subjects (Fagard et al 1984;Reimann & Frolich 1983) or in patients with severe leg ischaemia (data on file, No. [CSS = Ro/CL).…”

Pharmacodynamics and pharmacokinetics of single doses of ketanserin and propranolol alone and in combination in healthy volunteers.

“…In these subjects 20 mg ketanserin, a dose selected to avoid postural hypotension, had no effect on blood pressure or heart rate except standing diastolic blood pressure and this is similar to the effects observed in normotensive individuals by others (Fagard et al, 1984 Time after dose (h) Figure 5 Comparison of the effects (mean ± s.e. mean) of 80 mg propranolol (A), 20 mg ketanserin (A), placebo (0) and propranolol plus placebo (v) on exercise (3 min) heart rate, systolic blood pressure, diastolic blood pressure.…”

Ketanserin

“…Ketanserin also inhibits vasoconstrictor responses to norepinephrine and to histamine in blood vessels from various species including rat, rabbit, dog, and man (18,84,194,212,265,268). In isolated vascular tissues, ketanserin shifts the doseresponse curves for norepinephrine in a parallel manner without depressing the maximal contractile response (Fig.…”

“…It also improves capillary blood flow in the skin (unpublished data on file) and the lung (127) of patients with pregangrene and acute respiratory failure, respectively. Ketanserin blunts the rise in blood pressure during dynamic and isometric exercise; it attenuates the rise in heart rate during isometric but not during dynamic exercise (65,84,196,207,289). It does not impair exercise capacity (84).…”

“…There is no concomitant stimulation of aldosterone production (290). There is no evidence that ketanserin influences the sympathetic or the renin-angiotensin-aldosterone system during chronic oral treatment (84,294). Ketanserin has no effect on the release of pituitary hormones (prolactin, growth hormone, luteinizing hormone, adrenocorticotropic hormone, antidiuretic hormone), on thyroid function, or on plasma cortisol levels (unpublished data on file).…”